Clinical characteristics of iTTP episodes following COVID-19 vaccination
| . | All Median (range) or n (%) . | Patient #1 . | Patient #2 . | Patient #3 . | Patient #4 . | Patient #5 . | Patient #6 . | Patient #7 . | Patient #8 . | Patient #9 . | Patient #10 . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | 57 (20-70) | 36 | 54 | 60 | 60 | 38 | 68 | 66 | 70 | 22 | 20 |
| Sex | Woman: 5 (50) | Woman | Man | Woman | Woman | Man | Man | Man | Woman | Man | Woman |
| Previous medical history | SLE | iTTP | iTTP | MCTDiTTP | Ischemic strokes, hypertension | SLE | |||||
| Vaccine | BNT162b2 | mRNA1273 | BNT162b2 | BNT162b2 | BNT162b2 | BNT162b2 | ChAdOx1 | ChAdOx1 | BNT162b2 | BNT162b2 | |
| nCoV-19 | nCoV-19 | ||||||||||
| Dose | First: 8 (80) | First | First | First | First | Second | First | First | First | Second | First |
| Days since last dose | 15 (6-30) | 6 | 23 | 10 | 12 | 30 | 17 | 8 | 10 | 18 | 25 |
| Type of episode | First: 7 (70) | First | Relapse | Relapse | First | First | Relapse | First | First | First | First |
| Years since last episode* | 19 | 27 | 6 | ||||||||
| Clinical presentation | Bruising, headache | Bruising, diffuse mucocutaneous bleeding, headache, amnesia | Cerebellar syndrome | Cerebellar syndrome, aphasia, confusion, chest pain | Fever, headache, hemiparesis, bruising | Dizziness | Facial paralysis | Comahemiparesis | Coma, seizures, purpura, fever | SLE Flare: polyarthritis, erythema | |
| Biology at diagnosis | |||||||||||
| Hemoglobin, g/dL | 8.0 (6.5-11.5) | 10.0 | 11.5 | 10.8 | 6.5 | 6.6 | 10.9 | 7.9 | 8.0 | 6.8 | 5.3 |
| Platelets, ×109/L | 14 (6-39) | 10 | 17 | 27 | 20 | 9 | 39 | 11 | 6 | 10 | 51 |
| Schistocytes, % | 3 (1-6) | 3 | 2 | 2 | 6 | 5 | 1 | 4 | 2 | + | 3 |
| Creatinine, mg/dL | 0.95 (0.76-1.70) | 0.98 | 1.70 | 0.76 | 0.92 | 1.01 | 0.79 | 0.93 | 0.90 | 1.15 | 1.00 |
| Troponin elevated† | 7 (70) | + | + | + | + | + | + | — | + | — | — |
| Fibrinogen, g/L | 3 (2.4-6.7) | 2,8 | 2.4 | 3.0 | 3.6 | 2.9 | 3.0 | 6.7 | NA | NA | 3.7 |
| D-dimers, FEU | 1571 (726-3768) | 726 | NA | NA | NA | 3768 | NA | 1200 | 1942 | NA | NA |
| ADAMTS13 activity, % | <5 | <5 | <10 | 5 | <1 | 2 | <5 | 11‡ | 6 | <10 | |
| Anti-ADAMTS13 Abs§ | 0.5 BU/mL | 1.1 BU/mL | + | 52 U/mL | + | — | — | 140 U/mL | + | 50 U/mL | |
| Anti-PF4 Abs | — | NA | — | NA | — | NA | — | — | — | NA | |
| French score | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | |
| Treatment | |||||||||||
| TPE (number) | 4 (0-38) | 8 | 3 | 3 | 3 | 38 | 4 | 5 | 0 | 17 | 0 |
| Corticosteroids | 10 (100) | + | + | + | + | + | + | + | + | + | + |
| Rituximab | 8 (80) | + | + | + | — | + | + | + | + | + | — |
| Caplacizumab | 6 (60) | — | + | — | + | + | + | + | + | — | — |
| Others | 2 (20) | — | — | — | — | — | — | — | IVIg, plasma infusionǁ | — | Plasma infusionǁ |
| Outcome | Clinical remission | Clinical remission | Clinical remission | Clinical remission | Exacerbation under TPE, clinical remission | Clinical remission | Clinical remission | Death 2 mo after presentation | Clinical remission | Clinical remission | |
| Rechallenge | 1 (10) | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 |
| Vaccine | BNT162b2 |
| . | All Median (range) or n (%) . | Patient #1 . | Patient #2 . | Patient #3 . | Patient #4 . | Patient #5 . | Patient #6 . | Patient #7 . | Patient #8 . | Patient #9 . | Patient #10 . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age | 57 (20-70) | 36 | 54 | 60 | 60 | 38 | 68 | 66 | 70 | 22 | 20 |
| Sex | Woman: 5 (50) | Woman | Man | Woman | Woman | Man | Man | Man | Woman | Man | Woman |
| Previous medical history | SLE | iTTP | iTTP | MCTDiTTP | Ischemic strokes, hypertension | SLE | |||||
| Vaccine | BNT162b2 | mRNA1273 | BNT162b2 | BNT162b2 | BNT162b2 | BNT162b2 | ChAdOx1 | ChAdOx1 | BNT162b2 | BNT162b2 | |
| nCoV-19 | nCoV-19 | ||||||||||
| Dose | First: 8 (80) | First | First | First | First | Second | First | First | First | Second | First |
| Days since last dose | 15 (6-30) | 6 | 23 | 10 | 12 | 30 | 17 | 8 | 10 | 18 | 25 |
| Type of episode | First: 7 (70) | First | Relapse | Relapse | First | First | Relapse | First | First | First | First |
| Years since last episode* | 19 | 27 | 6 | ||||||||
| Clinical presentation | Bruising, headache | Bruising, diffuse mucocutaneous bleeding, headache, amnesia | Cerebellar syndrome | Cerebellar syndrome, aphasia, confusion, chest pain | Fever, headache, hemiparesis, bruising | Dizziness | Facial paralysis | Comahemiparesis | Coma, seizures, purpura, fever | SLE Flare: polyarthritis, erythema | |
| Biology at diagnosis | |||||||||||
| Hemoglobin, g/dL | 8.0 (6.5-11.5) | 10.0 | 11.5 | 10.8 | 6.5 | 6.6 | 10.9 | 7.9 | 8.0 | 6.8 | 5.3 |
| Platelets, ×109/L | 14 (6-39) | 10 | 17 | 27 | 20 | 9 | 39 | 11 | 6 | 10 | 51 |
| Schistocytes, % | 3 (1-6) | 3 | 2 | 2 | 6 | 5 | 1 | 4 | 2 | + | 3 |
| Creatinine, mg/dL | 0.95 (0.76-1.70) | 0.98 | 1.70 | 0.76 | 0.92 | 1.01 | 0.79 | 0.93 | 0.90 | 1.15 | 1.00 |
| Troponin elevated† | 7 (70) | + | + | + | + | + | + | — | + | — | — |
| Fibrinogen, g/L | 3 (2.4-6.7) | 2,8 | 2.4 | 3.0 | 3.6 | 2.9 | 3.0 | 6.7 | NA | NA | 3.7 |
| D-dimers, FEU | 1571 (726-3768) | 726 | NA | NA | NA | 3768 | NA | 1200 | 1942 | NA | NA |
| ADAMTS13 activity, % | <5 | <5 | <10 | 5 | <1 | 2 | <5 | 11‡ | 6 | <10 | |
| Anti-ADAMTS13 Abs§ | 0.5 BU/mL | 1.1 BU/mL | + | 52 U/mL | + | — | — | 140 U/mL | + | 50 U/mL | |
| Anti-PF4 Abs | — | NA | — | NA | — | NA | — | — | — | NA | |
| French score | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | |
| Treatment | |||||||||||
| TPE (number) | 4 (0-38) | 8 | 3 | 3 | 3 | 38 | 4 | 5 | 0 | 17 | 0 |
| Corticosteroids | 10 (100) | + | + | + | + | + | + | + | + | + | + |
| Rituximab | 8 (80) | + | + | + | — | + | + | + | + | + | — |
| Caplacizumab | 6 (60) | — | + | — | + | + | + | + | + | — | — |
| Others | 2 (20) | — | — | — | — | — | — | — | IVIg, plasma infusionǁ | — | Plasma infusionǁ |
| Outcome | Clinical remission | Clinical remission | Clinical remission | Clinical remission | Exacerbation under TPE, clinical remission | Clinical remission | Clinical remission | Death 2 mo after presentation | Clinical remission | Clinical remission | |
| Rechallenge | 1 (10) | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 |
| Vaccine | BNT162b2 |
Abs, antibodies; BU, Bethesda units; FEU, fibrinogen equivalent units; IVIg, intravenous immunoglobulins; MCTD, mixed connective tissue disease; NA, not available; PF4, platelet factor 4; SLE, systemic lupus erythematosus; TPE, therapeutic plasma exchange; +, yes; —, no.
Due to the long delay since the last episode, these patients no longer had regular follow-up; consequently, no recent ADAMTS13 activity before vaccination is available.
Defined as above the upper limit of normal value.
ADAMTS13 activity measurement was performed after initiation of immunosuppressive therapy.
The presence of anti-ADAMTS13 antibodies was assessed either as the titer of total autoantibodies (inhibitory and noninhibitory) using an enzyme-linked immunosorbent assay expressed in arbitrary units (U/mL; the value of at least 25 U/mL was considered positive) or as the titer of inhibitory antibodies using a Bethesda assay expressed in Bethesda units (BU/mL), with 1 BU corresponding to the amount of inhibitor in 1 mL of plasma neutralizing 50% of ADAMTS13 activity of control levels (the value of at least 1.0 BU/mL was assumed to be positive).
In these 2 patients, TPE was omitted. Patient #8 was very comorbid and TPE was deemed too invasive. Hence, ADAMTS13 replacement was performed with plasma infusion only. In patient #10, initial presentation was a lupus flare with mild features of thrombotic microangiopathy. Initial treatment only included high-dose corticosteroids, leading to a rapid improvement of both lupus symptoms and thrombocytopenia. Later, ADAMTS13 activity confirmed the diagnosis of iTTP, and only plasma infusion was added to corticosteroids until complete remission.